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Search Results: 1 - 10 of 2180 matches for " Hyunjin Yoon "
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Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica Serovar Typhimurium
Hyunjin Yoon,Jason E. McDermott,Steffen Porwollik,Michael McClelland,Fred Heffron
PLOS Pathogens , 2009, DOI: 10.1371/journal.ppat.1000306
Abstract: To cause a systemic infection, Salmonella must respond to many environmental cues during mouse infection and express specific subsets of genes in a temporal and spatial manner, but the regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 83 regulators inferred to play a role in Salmonella enteriditis Typhimurium (STM) virulence and tested them in three virulence assays (intraperitoneal [i.p.], and intragastric [i.g.] infection in BALB/c mice, and persistence in 129X1/SvJ mice). Overall, 35 regulators were identified whose absence attenuated virulence in at least one assay, and of those, 14 regulators were required for systemic mouse infection, the most stringent virulence assay. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint, we focused on these 14 genes. Transcriptional profiles were obtained for deletions of each of these 14 regulators grown under four different environmental conditions. These results, as well as publicly available transcriptional profiles, were analyzed using both network inference and cluster analysis algorithms. The analysis predicts a regulatory network in which all 14 regulators control the same set of genes necessary for Salmonella to cause systemic infection. We tested the regulatory model by expressing a subset of the regulators in trans and monitoring transcription of 7 known virulence factors located within Salmonella pathogenicity island 2 (SPI-2). These experiments validated the regulatory model and showed that the response regulator SsrB and the MarR type regulator, SlyA, are the terminal regulators in a cascade that integrates multiple signals. Furthermore, experiments to demonstrate epistatic relationships showed that SsrB can replace SlyA and, in some cases, SlyA can replace SsrB for expression of SPI-2 encoded virulence factors.
Early-type host galaxies of Type II and Ib Supernovae
Hyewon Suh,Sung-chul Yoon,Hyunjin Jeong,Sukyoung K. Yi
Physics , 2011, DOI: 10.1088/0004-637X/730/2/110
Abstract: Recent studies find that some early-type galaxies host Type II or Ibc supernovae (SNe II, Ibc). This may imply recent star-formation activities in these SNe host galaxies, but a massive star origin of the SNe Ib so far observed in early-type galaxies has been questioned because of their intrinsic faintness and unusually strong Ca lines shown in the nebular phase. To address the issue, we investigate the properties of early-type SNe host galaxies using the data with Galaxy Evolution Explore(GALEX) ultraviolet photometry, and the Sloan Digital Sky Survey (SDSS) optical data. Our sample includes eight SNe II and one peculiar SN Ib (SN 2000ds) host galaxies as well as 32 SN Ia host galaxies. The host galaxy of SN 2005cz, another peculiar SN Ib, is also analysed using the GALEX data and the NASA/IPAC Extragalactic Database (NED) optical data. We find that the NUV-optical colors of SN II/Ib host galaxies are systematically bluer than those of SN Ia host galaxies, and some SN II/Ib host galaxies with NUV-r colors markedly bluer than the others exhibit strong radio emission. We perform a stellar population synthesis analysis and find a clear signature of recent star-formation activities in most of the SN II/Ib host galaxies. Our results generally support the association of the SNe II/Ib hosted in early-type galaxies with core-collapse of massive stars. We briefly discuss implications for the progenitors of the peculiar SNe Ib 2000ds and 2005cz.
Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella
Hyunjin Yoon, Charles Ansong, Jason E McDermott, Marina Gritsenko, Richard D Smith, Fred Heffron, Joshua N Adkins
BMC Systems Biology , 2011, DOI: 10.1186/1752-0509-5-100
Abstract: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism.Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.The interactions between intracellular pathogen and host can be complex involving sophisticated offensive and defensive strategies by both organisms. Developing a systems level understanding of the virulence program of a pathogen, both in terms of the regulatory pathways and the virulence-related proteins that execute this program is important to effectively combat persistent and adapting pathogens [1-3]. Combining high-throughput characterization of proteins and gene transcripts under multiple different conditions relevant to virulence provides a wealth of information that can be mined to provide useful leads for further investigation or used as the basis of predictive models.Salmonella enterica serovar Typhimurium (STM) is a facultative intracellular bacterial pathogen with a broad host range capable of infecting birds, reptiles, mice, humans and other mammals. In humans, it is a leading causative agent
Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Translation
Charles Ansong, Hyunjin Yoon, Steffen Porwollik, Heather Mottaz-Brewer, Brianne O. Petritis, Navdeep Jaitly, Joshua N. Adkins, Michael McClelland, Fred Heffron, Richard D. Smith
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004809
Abstract: Using sample-matched transcriptomics and proteomics measurements it is now possible to begin to understand the impact of post-transcriptional regulatory programs in Enterobacteria. In bacteria post-transcriptional regulation is mediated by relatively few identified RNA-binding protein factors including CsrA, Hfq and SmpB. A mutation in any one of these three genes, csrA, hfq, and smpB, in Salmonella is attenuated for mouse virulence and unable to survive in macrophages. CsrA has a clearly defined specificity based on binding to a specific mRNA sequence to inhibit translation. However, the proteins regulated by Hfq and SmpB are not as clearly defined. Previous work identified proteins regulated by hfq using purification of the RNA-protein complex with direct sequencing of the bound RNAs and found binding to a surprisingly large number of transcripts. In this report we have used global proteomics to directly identify proteins regulated by Hfq or SmpB by comparing protein abundance in the parent and isogenic hfq or smpB mutant. From these same samples we also prepared RNA for microarray analysis to determine if alteration of protein expression was mediated post-transcriptionally. Samples were analyzed from bacteria grown under four different conditions; two laboratory conditions and two that are thought to mimic the intracellular environment. We show that mutants of hfq and smpB directly or indirectly modulate at least 20% and 4% of all possible Salmonella proteins, respectively, with limited correlation between transcription and protein expression. These proteins represent a broad spectrum of Salmonella proteins required for many biological processes including host cell invasion, motility, central metabolism, LPS biosynthesis, two-component regulatory systems, and fatty acid metabolism. Our results represent one of the first global analyses of post-transcriptional regulons in any organism and suggest that regulation at the translational level is widespread and plays an important role in virulence regulation and environmental adaptation for Salmonella.
Intervention to enhance skilled arm and hand movements after stroke: A feasibility study using a new virtual reality system
Jill Stewart, Shih-Ching Yeh, Younbo Jung, Hyunjin Yoon, Maureen Whitford, Shu-Ya Chen, Lei Li, Margaret McLaughlin, Albert Rizzo, Carolee J Winstein
Journal of NeuroEngineering and Rehabilitation , 2007, DOI: 10.1186/1743-0003-4-21
Abstract: Two participants with chronic post-stroke paresis and different levels of motor severity attended 12 training sessions lasting 1 to 2 hours each over a 3-week period. Behavior measures and questionnaires were administered pre-, mid-, and post-training.Both participants improved VR task performance across sessions. The less impaired participant averaged more time on task, practiced a greater number of blocks per session, and progressed at a faster rate over sessions than the more impaired participant. Impairment level did not change but both participants improved functional ability after training. The less impaired participant increased the number of blocks moved on the Box & Blocks test while the more impaired participant achieved 4 more items on the Functional Test of the Hemiparetic UE.Two participants with differing motor severity were able to engage in VR based practice and improve performance over 12 training sessions. We were able to successfully provide individualized, progressive practice based on each participant's level of movement ability and rate of performance improvement.Neurorehabilitation after stroke may include interventions designed to improve functional upper extremity (UE) skills through task-related practice. While amount of practice is an important variable for motor learning [1], variations in direction, timing and speed are needed to optimize the development of skill [2]. Virtual reality (VR) is a promising modality for the creation of favorable practice environments for neurorehabilitation [3-8].The purpose of this pilot trial was to determine the feasibility of providing individualized, progressive practice of skilled UE arm and hand movements after stroke using VR based tasks. We developed 4 tasks that allowed control of multiple parameters for the purpose of promoting motor skill learning by varying movement direction and speed. We investigated the feasibility of implementing an intervention tailored to each individual's level of movemen
CD11c+ Cells Partially Mediate the Renoprotective Effect Induced by Bone Marrow-Derived Mesenchymal Stem Cells
Myung-Gyu Kim, Su Hee Kim, Hyunjin Noh, Yoon Sook Ko, Hee Young Lee, Sang-Kyung Jo, Won Yong Cho, Hyoung Kyu Kim
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072544
Abstract: Previous studies have shown that induction of immune tolerance by mesenchymal stem cells (MSCs) is partially mediated via monocytes or dendritic cells (DCs). The purpose of this study was to determine the role of CD11c+ cells in MSC-induced effects on ischemia/reperfusion injury (IRI). IRI was induced in wildtype (WT) mice and CD11c+-depleted mice following pretreatment with or without MSCs. In the in-vitro experiments, the MSC-treated CD11c+ cells acquired regulatory phenotype with increased intracellular IL-10 production. Although splenocytes cocultured with MSCs showed reduced T cell proliferation and expansion of CD4+FoxP3+ regulatory T cells (Tregs), depletion of CD11c+ cells was associated with partial loss of MSCs effect on T cells. In in-vivo experiment, MSCs’ renoprotective effect was also associated with induction of more immature CD11c+ cells and increased FoxP3 expression in I/R kidneys. However all these effects induced by the MSCs were partially abrogated when CD11c+ cells were depleted in the CD11c+-DTR transgenic mice. In addition, the observation that adoptive transfer of WT CD11c+ cells partially restored the beneficial effect of the MSCs, while transferring IL-10 deficient CD11c+ cells did not, strongly suggest the important contribution of IL-10 producing CD11c+ cells in attenuating kidney injury by MSCs. Our results suggest that the CD11c+ cell-Tregs play critical role in mediating renoprotective effect of MSCs.
Current trends in the development and application of molecular technologies for cancer epigenetics
Hyeran Jang,Hyunjin Shin
World Journal of Gastroenterology , 2013, DOI: 10.3748/wjg.v19.i7.1030
Abstract: Current progress in epigenetic research supports the view that diet and dietary components are important in cancer etiology by enhancing or inhibiting carcinogenesis. Since diet and dietary factors may significantly contribute to the causation and progression of many cancers, it is important to find the molecular mechanisms of action of such dietary factors for cancer prevention and treatment. Recently, the role of epigenetic mechanisms in the cancer development and progression has attracted more attention as additional evidence along with traditional DNA sequence based mechanisms such as mutations and structural re-arrangements. Such an increasing interest in cancer epigenetics has also accelerated the development and application of molecular assays and tools for DNA methylation detection and histone modification enrichment analysis. In this paper, key assays and methods for epigenetic research are reviewed and discussed in terms of their utility and usability. In addition, more advanced methods for genome-wide analysis are introduced as part of upcoming research trends and directions.
Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium
Charles Ansong, Nikola Toli?, Samuel O Purvine, Steffen Porwollik, Marcus Jones, Hyunjin Yoon, Samuel H Payne, Jessica L Martin, Meagan C Burnet, Matthew E Monroe, Pratap Venepally, Richard D Smith, Scott N Peterson, Fred Heffron, Michael McClelland, Joshua N Adkins
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-433
Abstract: We experimentally annotated the bacterial pathogen Salmonella Typhimurium 14028, using "shotgun" proteomics to accurately uncover the translational landscape and post-translational features. The data provide protein-level experimental validation for approximately half of the predicted protein-coding genes in Salmonella and suggest revisions to several genes that appear to have incorrectly assigned translational start sites, including a potential novel alternate start codon. Additionally, we uncovered 12 non-annotated genes missed by gene prediction programs, as well as evidence suggesting a role for one of these novel ORFs in Salmonella pathogenesis. We also characterized post-translational features in the Salmonella genome, including chemical modifications and proteolytic cleavages. We find that bacteria have a much larger and more complex repertoire of chemical modifications than previously thought including several novel modifications. Our in vivo proteolysis data identified more than 130 signal peptide and N-terminal methionine cleavage events critical for protein function.This work highlights several ways in which application of proteomics data can improve the quality of genome annotations to facilitate novel biological insights and provides a comprehensive proteome map of Salmonella as a resource for systems analysis.Many aspects of modern biological research are dependent on accurate identification of the protein-coding genes in each genome, as well as the nature of the mature functional protein products, a process commonly referred to as genome annotation. With the exponential increase in the number of sequenced prokaryotic genomes afforded by advances in genome sequencing technologies over the last decade, present day prokaryotic genome annotation is essentially an automated high-throughput process that relies heavily on de novo gene prediction programs [1-3].While de novo gene prediction programs have significantly improved for prokaryotic genomes consider
Dissection of Halpha Emitters : Low-z Analogs of z>4 Star-Forming Galaxies
Hyunjin Shim,Ranga-Ram Chary
Physics , 2012, DOI: 10.1088/0004-637X/765/1/26
Abstract: Strong Halpha Emitters (HAEs) dominate the z~4 Lyman-break galaxy population. We have identified local analogs of these HAEs using the Sloan Digital Sky Survey (SDSS). At z<0.4, only 0.04% of galaxies are classified as HAEs with Halpha equivalent widths (>500A) comparable to that of z~4 HAEs. Local HAEs have lower stellar mass and lower ultraviolet (UV) luminosity than z~4 HAEs, yet the Halpha-to-UV luminosity ratio as well as their specific star-formation rate is consistent with that of z~4 HAEs indicating that they are scaled down versions of high-z star-forming galaxies. Compared to the previously studied local analogs of z~2 Lyman break galaxies selected using rest-frame UV, local HAEs show similar UV luminosity surface density, weaker Dn(4000) breaks, lower metallicity and lower stellar mass. This supports the idea that local HAEs are less evolved galaxies than the traditional Lyman break analogs. We are not able to constrain if the star-formation history in local HAEs is powered by mergers or by cosmological cold flow accretion. However, in the stacked spectrum, local HAEs show a strong HeII4686 emission line suggesting a population of young (<10Myr), hot, massive stars similar to that seen in some Wolf-Rayet galaxies. Low [NII]/[OIII] line flux ratios imply that local HAEs are inconsistent with being systems that host bright AGN. Instead, it is highly likely that local HAEs are galaxies with an elevated ionization parameter, either due to a high electron density or large escape fraction of hydrogen ionizing photons as in the case for Wolf-Rayet galaxies.
Outflows in Sodium Excess Objects
Jongwon Park,Hyunjin Jeong,Sukyoung K. Yi
Physics , 2015, DOI: 10.1088/0004-637X/809/1/91
Abstract: van Dokkum and Conroy revisited the unexpectedly strong Na I lines at 8200 A found in some giant elliptical galaxies and interpreted it as evidence for unusually bottom-heavy initial mass function. Jeong et al. later found a large population of galaxies showing equally-extraordinary Na D doublet absorption lines at 5900 A (Na D excess objects: NEOs) and showed that their origins can be different for different types of galaxies. While a Na D excess seems to be related with the interstellar medium (ISM) in late-type galaxies, smooth-looking early-type NEOs show little or no dust extinction and hence no compelling sign of ISM contributions. To further test this finding, we measured the doppler components in the Na D lines. We hypothesized that ISM would have a better (albeit not definite) chance of showing a blueshift doppler departure from the bulk of the stellar population due to outflow caused by either star formation or AGN activities. Many of the late-type NEOs clearly show blueshift in their Na D lines, which is consistent with the former interpretation that the Na D excess found in them is related with star formation-caused gas outflow. On the contrary, smooth-looking early-type NEOs do not show any notable doppler component, which is also consistent with the interpretation of Jeong et al. that the Na D excess in early-type NEOs is likely not related with ISM activities but is purely stellar in origin.
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